Nuclear DNA content and prognosis in human breast cancer: A static cytophotometric study (original) (raw)
Related papers
Journal of Clinical Pathology, 1999
Aim-To determine the importance of tumour DNA ploidy and cell proliferation, as measured by the S phase fraction (SPF), in relation to other established clinicopathological indicators of prognosis in breast cancer. Methods-A prospective study of 308 patients. Tumours were staged following the TNM system criteria and were classified according to the histological type and grade. DNA flow cytometry was performed on fresh/frozen samples stained with propidium iodide. Hormone receptors were analysed by immunocytochemistry. A Cox proportional hazards regression model was used for statistical evaluation of the prognostic factors. Results-Median follow up time was 39.6 months (range 3 to 84). A DNA diploid pattern was found in 134 tumours (43.5%) and aneuploid in 174 (56.5%). Median SPF value was 6.1% (range 1% to 27.8%). DNA ploidy and SPF were strongly correlated (p < 0.001), and both were related to histological type (p < 0.001), grade of diVerentiation (p < 0.001), tumour size (p = 0.006 and p = 0.002), and hormone receptor activity (p < 0.001). DNA ploidy was also related to node status (p = 0.022), but SPF was not. In univariate analysis, there were significant correlations between disease-free survival and age, histological grade, tumour size, node status, DNA ploidy, SPF, and hormone receptor activity; age, tumour size, node status, DNA ploidy, and hormone receptors were predictors of overall survival. In multivariate analysis, only node status (p = 0.001) and DNA ploidy (p = 0.006) retained independent prognostic significance in relation with overall survival, while node status (p < 0.001) and SPF (p < 0.001) were predictors of disease-free survival. DNA ploidy and SPF continued to predict disease-free and overall survival in lymph node positive (pN1) patients but not in the lymph node negative (pN0) group. Conclusions-DNA ploidy and SPF are strongly intercorrelated and have independent prognostic value for predicting the short term clinical outcome of breast carcinoma patients.
Relationship between DNA ploidy and survival in patients with primary breast cancer
British Journal of Surgery, 1989
The DNA ploidy of pancreatic cancer tissue from paraffin blocks was measured by flow cytometry in 46 patients whose disease had been detected and treated with surgery. Lymph node involvement was observed at the time of diagnosis in 36% of patients with diploid tumors and in 79% of patients with aneuploid tumors (p = 0.017), but no clear relation to metastasis could be observed (p = 0.201). The S-phase fraction (SPF) was significantly higher in aneuploid than in diploid tumors (p = 0.007). Ail patients who underwent radical surgery had diploid DNA content and SPF below the median (11.5%). Seven patients with a diploid tumor (32%) and none of the aneupioid cases survived 1 year. Over the 1-year period, in order of importance, the type of treatment (p < 0.001), DNA ploidy (p = 0.004), tumor size (p = 0.0046), and lymph node status (p = 0.027) predicted survival. Aneuploidy showed a significant association with decreased cumulative survival 0, = 0.015), and a suggestive relationship with SPF was found. The results suggest that DNA ploidy of pancreatic cancer can be used in dividing the patients into different prognostic groups. The value of the detection of aneuploidy, however, is limited, because diploid pancreatic cancers are also generally rapidly fatal.
Journal of Clinical Pathology, 2007
To investigate the role of DNA aneuploidy, particularly in patients with node negative breast cancer, in order to identify the different risk profiles within the pool of heterogeneous breast cancers. Methods: Imprint smears from 370 breast carcinomas were Feulgen-stained and measured by DNA image analysis. DNA aneuploidy was graded by the amount of aneuploid cells (DNA content .5c) and highly aneuploid cells (DNA content .9c) in a breast tumour population. These results were correlated to the clinical long-term follow-up. A statistical cutoff value of .10 aneuploid cells (.5c) and of .1 highly aneuploid cell (.9c) was evaluated as significant for disease-free survival (DFS) and overall survival (OS). Results: Subgroups among patients with breast cancer with aneuploid cells below the cutoff value showed a significantly longer DFS and OS than those with aneuploid cells above this value. Patients with node negative breast cancer with .10 aneuploid cells (.5c) and .1 highly aneuploid cell (.9c) showed an unfavourable prognosis similar to patients with node positive breast cancer with ,10 aneuploid cells (.5c) and ,1 highly aneuploid tumour cell (.9c) in DFS and OS. Conclusion: Nuclear DNA content, as an objective marker of tumour aggressiveness, provides prognostic information in patients with both node negative and node positive breast cancer. Based on DNA aneuploidy, the clinically inhomogeneous group of patients with node negative breast cancer can be stratified into low-risk and high-risk subgroups. Therefore, DNA ploidy analysis may identify high-risk patients with lymph node negative breast cancer who might benefit from additional adjuvant therapy.
Relationship of DNA Ploidy and S-Phase Fraction to Survival After First Recurrence of Breast Cancer
Acta Oncologica, 1994
Flow cytometry was performed on frozen specimens from the primary tumour of 184 women with recurrent breast cancer. No significant association was seen between DNA ploidy and the other prognostic factors investigated. Patients with a high S-phase fraction had more often a negative estrogen receptor (ER) status and a short disease-free interval. A shorter survival after disease recurrence was seen both in patients with DNA aneuploid tumours and among those with a high S-phase fraction. Patients with DNA tetraploid tumours showed the longest survival after recurrence. In this subgroup, half of the patients survived more than 3 years after recurrence and the estimated survival rate at 10 years was 17%. In a Cox's regression analysis including 116 patients, site of recurrence, number of positive nodes at time of primary operation, size and ER content of the primary tumour as well as DNA ploidy showed additional prognostic value.
Characterization of breast cancer DNA content profiles as a prognostic tool
Experimental oncology, 2014
Worldwide, breast cancer in women remains to be the most common malignancy that in a considerable proportion shows the resistance to genotoxic treatments and poor outcome. Chromosomal instability manifested as aneuploidy represents an integral cha-racteristics of the malignant genotype not only because of the selection of mutated aneuploid sub-clones that stipulate the tumor progression, but also because of the reversible endopolyploidy of tumor cells that serves for the endless maintenance of therapy-resistant tumor stem cells. Therefore, cytometric determination of DNA content in tissue samples for detecting malignancy, monitoring responses to therapy, and prognosing disease outcome needs to be revived. Both flow and image cytometry are most frequently used for generation of DNA content profiles (histograms), interpretation of which, however, may have some caveats. This review presents the major characterization criteria and analysis tools for breast cancer DNA histograms.
Analysis of DNA and morphometry in breast carcinoma
Histochemistry and Cell Biology, 1996
Feulgen-stained imprints and smears from 730 cases of invasive breast cancer were investigated using an image analysis system. From each tumor sample 100 cells were randomly scanned and several DNA and morphometrical parameters evaluated. Their prognostic value for a prediction of distant metastases within 5 years was investigated with the multivariate Cox regression analysis, which was performed for all consecutive cases, as well as for node-negative and node-positive patients separately. The multivariate analyses showed a strong prognostic value of the anisonucleosis (variation of nuclear radius) and the DNA histogram type in addition to the nodal status, the tumor size (pT), and the histological tumor grade. However, performing this analysis for both node-positive patients and for those without lymph node metastases demonstrated a different prognostic meaning of the variables. The combination of each of the group-specific variables led to a prognostic factor, which allowed an assignment of patients to several subgroups with significantly different risk for distant metastases. Thus, both a low-risk group of node-negative patients with a 5-year distant recurrence rate of only 5.8%, and a higher risk group of node-negative patients with a recurrence rate of 38.6% could be identified. Among the node-positive patients, a low-risk group with a distant recurrence rate of 8.6%, and also a high risk group with
Effect of DNA ploidy classification on prognosis in breast cancer
International Journal of Cancer, 1992
A series of 327 breast cancers was analyzed for DNA ploidy by flow cytometry from paraffin-embedded tissue, and the resulting DNA histograms were classified independently by 6 researchers in the field as DNA diploid (Di), aneuploid (An), tetraploid (Te), multiploid (Mu), or technically uninterpretable. The frequency of diploid, aneuploid, tetraploid and multiploid cancers varied from 28 to 41%, 33 to 49%, 8 to 21% and 2 to 6%. According to the scale Di-An-Te-Mu, DNA ploidy was not significantly associated with breast-cancer mortality by 2 classifiers, but if DNA euploid cancers (Di+Te) were tested against non-euploid, or diploid cancers against non-diploid, all classifiers found DNA euploid and diploid cancers to have better prognosis. Mortality associated with diploid or tetraploid cancers decreased with improving histogram quality and increasing uniformity of classification, whereas that associated with aneuploid cancers remained unaltered. Among the cases where all classifiers agreed on ploidy, tetraploid, diploid and aneuploid cancers were associated with 100%, 88% and 68% 5-year survival rates. In this sub-set the S-phase fraction and possibly DNA ploidy were independent prognostic factors, together with histological grade, axillary node status, and primary tumor size. © 1992 Wiley-Liss, Inc.
Intratumoral variations in DNA ploidy and s-phase fraction in human breast cancer
Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology, 2001
To study intratumoral DNA ploidy heterogeneity and S-phase fraction (SPF) variability, we prospectively collected five different samples from 48 breast carcinomas and each sample was analysed separately by flow cytometry. Aneuploidy rate was 89.6% after analysis of four or five samples. DNA ploidy heterogeneity, i.e., different samples classified as either DNA euploid or DNA aneuploid in the same tumor was seen in 17%, and DNA index heterogeneity, i.e., tumor populations with different DNA indices (DIs) seen in different samples was 44%. A statistical model defining SPF heterogeneity is proposed. SPF heterogeneity as defined by us was 71%, and as expected the SPF heterogeneity rate increased significantly with increasing number of analysed samples. Four or more samples are needed to detect the most deviant (highest) SPF values. An unrecognized intratumor heterogeneity of DNA ploidy and SPF may partly explain the conflicting results reported in the literature on the above prognostic ...
Acta Oncologica, 1994
We studied histological samples and clinical data from 11 1 breast carcinoma patients originally treated in 1975-1977 who did not have distant metastases at the time of diagnosis. A multivariate survival analysis using the Cox model selected the studied variables in the following order according to their prognostic association (breast cancer deaths, or deaths from any cause): axillary lymph node status, tumor size, mitotic index, and DNA ploidy status. The association of the different variables to the prognosis in respect to breast cancer deaths was evaluated 1-10 years after treatment by stepwise logistic regression. Lymph node status, tumor size, mitotic index, and DNA ploidy all showed significant relation to the prognosis but this association varied considerably with time of observation. Numerous approaches have been tried to find suitable prognostic indicators in breast cancer (1-13). Most studies have concerned histologic parameters with the best results obtained by mitotic counts (3, DNA cytometry showing association between ploidy and prognosis in different materials (9, 13-25), and clinical variables revealing the great importance of axillary lymph node status and primary tumor size (3-28). Baak et al. (5) showed that a combination of mitotic index, tumor size, and lymph node status in a multivariate prognostic index had a good predictive ability. This has been verified in our own study (1 I). and we also found that good prognostic prediction was obtained by a multivariate index created by combining DNA ploidy and prognostically important clinical variables (13). We have now combined these two approaches to see